Regioselective Addition of Grignard Reagents to 1-Acylpyridinium Salts. A Convenient Method for the Synthesis of 4-Alkyl(aryl)pyridines

Article abstract of DOI:10.1021/jo00143a028

The addition of Grignard reagents to 1-acylpyridinium salts afforded 1-acyl-2-alkyl(aryl)-1,2-dihydropyridines and 1-acyl-4-alkyl(aryl)-1,4-dihydropyridines.The regioselectivity of this reaction, 1,2- vs. 1,4-addition, was examined and found to be dependent upon the structures of the Grignard reagent and the 1-acyl group.Pyridine, 2-picoline, and 3-picoline were studied, and in most cases, significant amounts of 1,4-addition occurred.When a catalytic amount of cuprous iodide was present, nearly exclusive 1,4-addition resulted.The crude 1,4-dihydropyridines were aromatized by heating with sulfur to provide 4-substituted pyridines and picolines in good yield and high isomeric purity.